Gene targeting is a technique to introduce genetic change into specific locations in the genome of a cell. The targeted introduction of genetic changes can be used as a powerful experimental approach and as a therapeutic technique for ameliorating genetic aspects of disease. Gene targeting is widely used in murine embryonic stem cells (ES cells) and certain other specialized cell types such as chicken B-cell line DT40 to facilitate research on the genetic control of many processes. Gene targeting also represents a potentially powerful way of performing gene therapy. More than 3,000 diseases are caused by mutations such as, for example, hemophilia, Tay-Sachs disease, Duchenne's muscular dystrophy, Huntington's disease, alpha-thalassemia, Lesch Nyhan syndrome, etc. Most of these diseases cannot be treated medically. If gene targeting could be harnessed for use in humans, it could be used to correct many of these genetic diseases.
It is known that genes introduced into mammalian cells integrate into the DNA of the cell primarily at non-homologous sites. Thus, instead of replacing a mutated gene, the wild type copy will be introduced at another locus in the DNA. In the cell types that have been used for gene therapy, the rate of gene targeting is extremely low. Therefore, there is a need to develop a technique to increase the efficiency of gene targeting so that it can be used in cell types for experimental and therapeutic purposes including gene therapy.